The Mayo Clinic Breast Cancer SPORE is being submitted by the Mayo Clinic Cancer Center (MCCC) and Mayo Foundation. This application supports a multidisciplinary team of basic, clinical and population science investigators to perform translational research directed at reducing the burden and mortality from breast cancer. The translational research projects chosen represent extensions of funded research being conducted by SPORE investigators. The science of the SPORE consists of four translational research projects. Project 1 "The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast Cancer" examines Chfr, a polypeptide involved in a novel mitotic checkpoint pathway. This project will elucidate the molecular role of Chfr in the control of mitotic progression, examine its contribution to development of breast cancer and evaluate it as a predictive factor in women with metastatic breast cancer treated with paclitaxel. Project 2 "BRCA2 Missense Mutations and Breast Cancer" addresses the critically important question of which BRCA2 missense mutations predispose to cancer and which are neutral. These studies involve development of risk assessment models using genetic and functional assay data and will be directly translatable to patients with these mutations. Project 3 "Preclinical and Clinical Studies of MUC1 Glycopeptide Vaccine Strategies in Breast Cancer" is directed at developing an optimal breast-cancer based vaccine utilizing glycosylated peptides derived from the MUC1 sequence, which is over expressed and aberrantly glycosylated in over 90% of breast cancers. Project 4 "Aromatase Inhibitors, Breast Density and Plasma Steroid Hormones" evaluates the impact of aromatase inhibitor (Al) therapy on mammographic breast density in women in relation to plasma levels of the Al and steroid hormones and will examine pharmacogenetic associations of haplotype single nucleotide polymorphisms in the cytochrome P450 enzyme system. These research projects will be supported by three cores: Core 1: SPORE Administration, Core 2: Biospecimens and Patient Registry, and Core 3: Biostatistics. A Developmental Research Program has been established to develop promising research initiatives and a Career Development Program will be used to promote the research and career of the most promising junior faculty investigators in breast cancer translational research. The investigators, core facilities, and the developmental research programs in the SPORE are all integrated into the MCCC and, collectively, will advance knowledge and translate findings into the clinic for the benefit of women with breast cancer.